Nektar Therapeutics (NKTR) 2026 Q1 法說會逐字稿

Hello, and thank you for standing by. Welcome to the Nektar Therapeutics first-quarter 2026 financial results conference call. (Operator Instructions) Please be advised that today's conference call is being recorded.

您好，感謝各位稍候。歡迎參加 Nektar Therapeutics 2026 年第一季財務業績電話會議。(接線員指示) 請注意，今天的電話會議將被錄音。

I would now like to hand the conference over to Vivian Wu from Nektar Investor Relations to kick things off. Please go ahead.

現在我想把會議交給 Nektar 投資人關係部的 Vivian Wu 來開始。請開始。

Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. On today's call, you will hear from Howard Robin, our President and Chief Executive Officer; Dr. Jonathan Zalevsky, our Chief Research and Development Officer; and Sandra Gardiner, our Chief Financial Officer. Dr. Mary Tagliaferri, our Chief Medical Officer, will also be available during the Q&A.

謝謝你，Crystal，各位下午好。感謝各位今天加入我們。在今天的電話會議中，您將聽到我們的總裁暨執行長 Howard Robin、研發長 Jonathan Zalevsky 博士，以及財務長 Sandra Gardiner 的發言。我們的醫務長 Mary Tagliaferri 博士也將在問答環節中出席。

Before I begin, I would like to remind you that we will be making forward-looking statements regarding our business, including statements related to the therapy potential and development plans for rezpegaldesleukin, the timing and expectations for clinical data presentations, regulatory interactions, and other statements regarding the future of our business. Because forward-looking statements relate to the future, they are subject to uncertainties and risks that are difficult to predict and many of which are outside of our control. For a discussion of these risks and uncertainties, please refer to our filings with the SEC, including our most recent Form 10-K and subsequent filings. We undertake no obligation to update these forward-looking statements, except as required by law. A live webcast and replay of this call will be available on the Investor Relations section of our website at nektar.com.

在我開始之前，我想提醒各位，我們將就本公司業務發表前瞻性陳述，包括與 rezpegaldesleukin 的治療潛力與開發計畫、臨床數據發表的時程與預期、與監管機構的互動，以及其他關於本公司未來業務的陳述。由於前瞻性陳述涉及未來，因此會受到難以預測的不確定性與風險影響，其中許多因素超出我們的控制範圍。關於這些風險與不確定性的討論，請參閱我們向美國證券交易委員會（SEC）提交的文件，包括最新的 Form 10-K 以及其後續申報文件。除法律要求外，我們不承擔更新這些前瞻性陳述的義務。本次電話會議的即時網路直播與重播將可於我們網站 nektar.com 的投資人關係專區取得。

With that, I will turn the call over to Howard.

接下來，我把電話交給 Howard。

Thank you, Vivian, and good afternoon, everyone. We are exceptionally proud of the progress we've made at the company. The data we've reported over the last year from our Phase 2b studies in atopic dermatitis and alopecia areata demonstrate that REZPEG could produce clinically meaningful outcomes in two distinct autoimmune and inflammatory disease settings. Importantly, the data sets reported in February and April of this year highlight the potential for REZPEG to offer further improvement for patients over time.

謝謝你，Vivian，各位下午好。我們對公司所取得的進展感到無比自豪。我們在過去一年於異位性皮膚炎與圓形禿的第 2b 期研究中所公布的數據顯示，REZPEG 有望在兩種不同的自體免疫與發炎性疾病情境中帶來具臨床意義的結果。重要的是，我們在今年 2 月與 4 月所報告的數據集突顯了 REZPEG 隨時間推移可為患者帶來進一步改善的潛力。

In February of this year, we reported the long-term monthly and quarterly dosing results from the 36-week maintenance portion of REZOLVE-AD in patients with atopic dermatitis. These data showed a significant durability and further deepening of efficacy and established a highly differentiated profile for REZPEG as a novel regulatory T cell mechanism. Supported by these results, we're moving quickly to initiate the ZENITH-AD Phase 3 program in patients with moderate to severe atopic dermatitis by July of this year. We have completed our meetings with regulatory authorities on the Phase 3 program, and JZ will discuss the elements of the program later in the call. We expect to have the first data from the Phase 3 program in mid-2028, and this will support our goal of submitting a BLA in 2029.

今年 2 月，我們公布了 REZOLVE-AD 研究中異位性皮膚炎患者於 36 週維持治療部分的長期每月與每季給藥結果。這些數據顯示療效具有顯著的持久性，且療效進一步加深，並為 REZPEG 作為一種新穎的調節性 T 細胞機制建立了高度差異化的特徵。在這些結果的支持下，我們正快速推進，計畫於今年 7 月前在中重度異位性皮膚炎患者中啟動 ZENITH-AD 第 3 期計畫。我們已完成與監管機關就第 3 期計畫的會議，JZ 將在稍後的電話會議中討論該計畫的要素。我們預期將於 2028 年年中取得第 3 期計畫的首批數據，並支持我們在 2029 年提交 BLA 的目標。

There remains a need for novel mechanisms in atopic dermatitis beyond those currently available in the treatment landscape. In the US, there are over 15 million people with moderate to severe atopic dermatitis, and fewer than 10% are receiving biologic treatments for this chronic skin disorder with many patients not responding well to the existing agents. Roughly half of patients on existing approved agents, which includes Dupixent and other IL-13 based mechanisms, failed to respond or lose treatment effect over time. This leaves a significant opportunity for REZPEG to enter the treatment paradigm in a lead position as a novel immune modulating mechanism that could offer in both naive and experienced patients, a differentiated efficacy and safety profile and monthly or quarterly long-term maintenance dosing.

在異位性皮膚炎領域，除了目前治療版圖中既有的機制之外，仍需要新穎的作用機制。在美國，中重度異位性皮膚炎患者超過 1,500 萬人，而接受生物製劑治療這種慢性皮膚疾病的患者不到 10%，且許多患者對現有藥物反應不佳。使用現有已核准藥物（包括 Dupixent 及其他以 IL-13 為基礎的機制）的患者中，約有一半未能反應或隨時間推移而喪失治療效果。這為 REZPEG 帶來顯著機會，使其以新穎的免疫調節機制在治療模式中取得領先地位，並可在初治與既治患者中提供具差異化的療效與安全性特徵，以及每月或每季的長期維持給藥。

Turning to alopecia areata. In April, we announced positive 52-week top-line results from the blinded treatment extension period in the Phase 2 REZOLVE-AA study. These data also demonstrated a deepening of efficacy and clinically meaningful improvement across numerous SALT measurements with twice monthly dosing of REZPEG. We believe REZPEG can now be advanced as a compelling first-in-class biologic candidate that can change the treatment paradigm for patients with this condition. Nearly 6.7 million people in the US have alopecia areata, and the vast majority are untreated. More than half of dermatologists have been reluctant to prescribe the only approved systemic therapies, JAK inhibitors, because of box warnings and ongoing clinical monitoring challenges.

接著談圓形禿。今年 4 月，我們公布了第 2 期 REZOLVE-AA 研究在盲態治療延伸期間的 52 週正向主要結果。這些數據亦顯示，在每月兩次給藥 REZPEG 的情況下，療效進一步加深，並在多項 SALT 指標上呈現具臨床意義的改善。我們相信，REZPEG 現在可作為具吸引力的同類首創（first-in-class）生物製劑候選藥物推進，並有望改變此疾病患者的治療模式。美國約有 670 萬人罹患圓形禿，而其中絕大多數未接受治療。由於黑框警語以及持續臨床監測的挑戰，超過一半的皮膚科醫師一直不願開立唯一已核准的全身性治療——JAK 抑制劑。

We know there remains an unmet need for an efficacious and safe biologic with a better safety, efficacy, and dosing profile. Based on our KOL enthusiasm and market research, we believe there's a strong opportunity for REZPEG to capture frontline share in this indication. We plan to initiate the Phase 3 program in alopecia areata in the first part of 2027 to add a second potential indication to Nektar's BLA submission for REZPEG.

我們知道，市場仍存在對療效佳且安全的生物製劑之未被滿足需求，且需要更優的安全性、療效與給藥特徵。根據我們與關鍵意見領袖（KOL）的交流熱度以及市場研究，我們相信 REZPEG 在此適應症上有很強的機會取得第一線用藥市占。我們計畫於 2027 年上半年啟動圓形禿的第 3 期計畫，為 Nektar 的 REZPEG BLA 申請新增第二個潛在適應症。

The global markets for atopic dermatitis and alopecia areata combined are expected to reach close to $40 billion over the next five years. And we believe that this market has the potential to grow even further with the adoption of novel mechanisms like REZPEG. We've seen this with the introduction of new mechanisms in the psoriasis market over time, where the number of patients served grew tenfold over the span of 15 years and now supports 7 blockbuster products. That growth was not only driven by drugs competing for the same patients. Each new mechanism brought in new adopting treatment physicians who are not yet prescribing systemic therapies, and we believe atopic dermatitis and alopecia areata could be at a similar inflection point today. And as a truly novel MOA, we believe REZPEG can transform the treatment paradigm in both these indications. And importantly, we believe that Treg biology and REZPEG has potential application beyond atopic dermatitis and alopecia areata.

異位性皮膚炎與圓形禿的全球市場合計，預期在未來五年將接近 400 億美元。我們也相信，隨著像 REZPEG 這類新穎機制的採用，該市場仍有進一步成長的潛力。我們已在乾癬市場隨時間導入新機制的過程中看到這一點：在 15 年期間，受治療的患者人數成長了 10 倍，並且如今支撐了 7 項重磅產品（blockbuster）。這樣的成長不僅是藥物彼此競爭同一批患者所驅動。每一種新機制都帶來新的採用醫師族群——這些醫師先前尚未開立全身性治療；我們相信異位性皮膚炎與圓形禿在今天也可能正處於類似的拐點。作為真正新穎的作用機轉（MOA），我們相信 REZPEG 能在這兩個適應症中改變治療模式。而且重要的是，我們相信 Treg 生物學與 REZPEG 的應用潛力不僅限於異位性皮膚炎與圓形禿。

Nektar is now in a very strong financial position to support the advancement of REZPEG. Since year-end, we've raised approximately $783 million in net proceeds through two financings. We ended the first quarter of 2026 with $731 million in cash, and this does not include our April financing, which adds another $350 million to our balance sheet, bringing total cash and investments today to over $1 billion. With this financial strength, we could advance into Phase 3 in both indications with a cash runway that brings us into the third quarter of 2028, well past anticipated data readouts.

Nektar 目前具備非常強健的財務狀況，可支持 REZPEG 的推進。自去年年底以來，我們透過兩次融資籌得約 7.83 億美元的淨收益。我們在 2026 年第一季末的現金為 7.31 億美元，且此數字尚未包含我們 4 月的融資；該融資為資產負債表再增加 3.5 億美元，使得目前現金與投資總額超過 10 億美元。憑藉這樣的財務實力，我們可在兩個適應症上推進至第 3 期，並擁有可支撐至 2028 年第三季的現金跑道，遠超過預期的數據讀出時間點。

I'll now turn the call over to JZ to go over our clinical programs in more detail. JZ?

接下來我把電話交給 JZ，請他更詳細說明我們的臨床計畫。JZ？

Thank you, Howard. Good afternoon, everyone. As Howard said, over the past year, our clinical data generated from the REZOLVE-AD and REZOLVE-AA studies have confirmed that our approach with REZPEG to stimulate regulatory T cells translates into a differentiated clinical profile, compelling efficacy, a favorable safety profile, extended dosing frequency, and responses that deepen over time. Unlike therapies that block a single inflammatory pathway downstream, REZPEG acts upstream, restoring the fundamental immune balance that is disrupted in autoimmune and inflammatory diseases.

謝謝你，Howard。各位下午好。如 Howard 所說，在過去一年中，我們從 REZOLVE-AD 與 REZOLVE-AA 研究所產生的臨床數據已確認，我們以 REZPEG 刺激調節性 T 細胞的策略，能轉化為具差異化的臨床特徵、令人信服的療效、良好的安全性特徵、更長的給藥間隔，以及隨時間加深的反應。不同於僅在下游阻斷單一發炎途徑的療法，REZPEG 作用於上游，恢復在自體免疫與發炎性疾病中被破壞的基本免疫平衡。

Last June, we reported the 16-week induction period in the REZOLVE-AD study, in which REZPEG demonstrated a rapid onset of efficacy on key metrics of EASI-75 and itch. REZPEG also achieved statistical significance on the primary endpoint of mean percent change in EASI score and for the high dose, met statistical significance on all key secondary endpoints at week 16.

去年6月，我們公布了 REZOLVE-AD 研究中為期16週的誘導期結果，其中 REZPEG 在 EASI-75 與搔癢等關鍵指標上展現快速起效的療效。REZPEG 亦在主要終點（EASI 分數平均百分比變化）達到統計顯著性；且在高劑量組，於第16週在所有關鍵次要終點上皆達到統計顯著性。

In the 24-week crossover data of patients originally assigned to placebo and crossover to treatment with high dose REZPEG Q2 week, we saw further deepening of response with no sign of plateau. These data bolstered our decision to advance a 24-week induction period into Phase 3. In the 36-week maintenance phase, where patients continued on to less frequent monthly and quarterly dosing of REZPEG, we continued to see durability of the induction responses and observed increased responses for EASI-75, 90, vIGA, and itch over time. This also included up to a fivefold increase in EASI-100 rates, which represents complete skin clearance, a level of response rarely achieved for patients.

在原先分配至安慰劑、後交叉轉換為每兩週一次（Q2 週）高劑量 REZPEG 治療之患者的24週交叉資料中，我們觀察到反應進一步加深，且未見平台期跡象。這些資料強化了我們將24週誘導期推進至第3期的決策。在36週維持期中，患者改為較低頻率的每月與每季 REZPEG 給藥，我們持續看到誘導期反應的持久性，且 EASI-75、90、vIGA 與搔癢等指標的反應隨時間增加。其中亦包括 EASI-100 比例最高提升至五倍；EASI-100 代表皮膚完全清除，這是患者很少能達到的反應水準。

A key differentiating finding from our REZOLVE-AD study was the improvement in patient-reported comorbid asthma. Approximately 25% of patients with moderate to severe atopic dermatitis also have asthma and most approved therapies do not address this comorbidity. REZPEG produced statistically significant improvements in the asthma control questionnaire or ACQ-5 scores at week 16 versus placebo, including in patients with uncontrolled asthma at baseline. Outside of Dupixent, no other approved agent or late-stage candidate has demonstrated this. We are including ACQ-5 as a secondary endpoint in the Phase 3 program with the goal of potentially including this in the label.

REZOLVE-AD 研究的一項關鍵差異化發現，是患者自述之共病氣喘獲得改善。約25%的中重度異位性皮膚炎患者亦患有氣喘，而多數已核准療法無法處理此共病。REZPEG 在第16週相較安慰劑，使氣喘控制問卷（ACQ-5）分數出現統計顯著改善，包括基線時氣喘未受控制的患者。除 Dupixent 外，尚無其他已核准藥物或後期候選藥物證實此點。我們在第3期計畫中將 ACQ-5 納入次要終點，目標是未來可能將其納入標籤適應症說明。

In Q1 of 2027, we expect to report 52-week off-treatment data from REZOLVE-AD. These data will allow us to assess the remittent potential of REZPEG beyond 52 weeks, and we are looking forward to those data. We have completed the end of Phase 2 meeting with the FDA and the scientific advice process with the EMA, and we will initiate the first trial in the global Phase 3 program by July of this year.

我們預期於2027年第一季公布 REZOLVE-AD 的52週停藥後資料。這些資料將使我們得以評估 REZPEG 在52週之後的緩解（remittent）潛力，我們也期待看到這些結果。我們已完成與 FDA 的第2期結束（End of Phase 2）會議，以及與 EMA 的科學諮詢流程，並將於今年7月前啟動全球第3期計畫的首項試驗。

Our planned registrational program called ZENITH-AD is expected to include three trials in total, two global monotherapy studies with 510 biologic-naive patients 12 years and older in each study, along with a separate study in 510 treatment-experienced patients 12 years and older. For the two pivotal biologic naive studies, patients will be randomized 2:1 to receive 24 micrograms per kilogram every two weeks or placebo during a 24-week induction phase to be followed by a 28-week maintenance period, evaluating monthly and quarterly dosing regimens through week 52. The overall design is intended to be consistent with prior registrational studies supporting approval of biologics in atopic dermatitis.

我們規劃的註冊性計畫 ZENITH-AD 預計共包含三項試驗：兩項全球單藥研究，每項納入510名12歲以上、未使用過生物製劑（biologic-naive）的患者，另有一項獨立研究納入510名12歲以上、曾接受治療（treatment-experienced）的患者。在兩項關鍵的生物製劑未治療研究中，患者將以2:1隨機分派，在24週誘導期接受每兩週一次、每公斤24微克的治療或安慰劑；之後進入28週維持期，評估每月與每季給藥方案至第52週。整體設計旨在與先前支持異位性皮膚炎生物製劑核准的註冊性研究保持一致。

The first two studies in biologic naive patients will begin first starting in July of this year, and the third study in biologic experience will initiate a few months after that. Our market research supports usage of REZPEG as a first-line and second-line biologic therapy, and we have designed the program to capture this in the potential label. In addition to these 3 pivotal Phase 3 studies, the program will also contain other studies to support registration. These will also include a 200-patient open-label adolescent study and a long-term extension study. Additionally, we plan to launch REZPEG with an auto-injector and the BLA submission will also include a PK bridging study to support this.

前兩項針對生物製劑未治療患者的研究將於今年7月率先開始，第三項針對曾使用生物製劑/具治療經驗患者的研究將在數個月後啟動。我們的市場研究支持將 REZPEG 作為第一線與第二線生物製劑治療使用，因此我們設計此計畫以在潛在標籤中反映此定位。除這3項關鍵第3期試驗外，計畫亦將包含其他支持註冊的研究。其中也包括一項200名患者的開放標籤青少年研究，以及一項長期延伸研究。此外，我們計畫以自動注射器推出 REZPEG，而 BLA 申請亦將納入一項 PK 橋接研究以支持此項配置。

The agency is not requiring a vaccine study that has been done in some prior Phase 3 programs in this indication. The Phase 3 studies are designed to support both US and EU registration with an IGA-related primary endpoint for US registration and an EASI-75 coprimary endpoint to support European approval. A series of multiplicity protected endpoints for itch and other important patient-reported outcome measures such as sleep, quality of life, and asthma control are designed into the studies as well. We expect a similar country distribution as Phase 2 with the addition of other selected countries in Asia to reflect the global footprint. As Howard stated, we expect the first data readout from the Phase 3 program in the middle of 2028.

主管機關並未要求進行疫苗研究；在此適應症的一些既往第3期計畫中曾做過此類研究。第3期研究設計旨在同時支持美國與歐盟註冊：以與 IGA 相關的主要終點支持美國註冊，並以 EASI-75 共同主要終點（coprimary endpoint）支持歐洲核准。研究亦納入一系列具多重性（multiplicity）控制保護的終點，涵蓋搔癢及其他重要的患者自述結果指標，例如睡眠、生活品質與氣喘控制。我們預期國家分布將與第2期相近，並新增亞洲其他特定國家以反映全球布局。如 Howard 所述，我們預期第3期計畫的首次資料讀出將在2028年年中。

Moving now to alopecia areata. We recently reported the 52-week top-line results from the blinded 16-week treatment extension of our Phase 2b REZOLVE-AA study. As a reminder, our Phase 2b REZOLVE-AA trial enrolled 92 adult patients with severe to very severe alopecia areata. Patients received subcutaneous REZPEG in 24 micrograms per kilogram every 2 weeks, 18 micrograms per kilogram every 2 weeks or placebo. The primary and key secondary endpoints were assessed at the end of the 36-week induction period, which we reported last December. These data demonstrated a proof of concept in alopecia areata and showed that REZPEG met the target product profile of standard of care low-dose JAK inhibitor. The extension phase was specifically designed to evaluate whether continued treatment with REZPEG beyond week 36 could drive additional patients to achieve a SALT score 20 response. SALT score 20 represents a patient achieving 80% or more scalp hair coverage, which is the established registrational endpoint in alopecia areata.

接下來談圓形禿（alopecia areata）。我們近期公布了第2b期 REZOLVE-AA 研究中、盲態16週治療延伸的52週主要（top-line）結果。提醒一下，我們的第2b期 REZOLVE-AA 試驗納入92名重度至極重度圓形禿成人患者。患者接受皮下 REZPEG：每兩週一次、每公斤24微克；或每兩週一次、每公斤18微克；或安慰劑。主要與關鍵次要終點於36週誘導期結束時評估，我們已於去年12月公布。這些資料證實圓形禿的概念驗證（proof of concept），並顯示 REZPEG 符合目標產品概況（TPP），可達到標準治療的低劑量 JAK 抑制劑水準。延伸期特別設計用以評估：在第36週之後持續以 REZPEG 治療，是否能促使更多患者達到 SALT 分數20的反應。SALT 分數20代表患者頭皮毛髮覆蓋率達80%或以上，為圓形禿既定的註冊性終點。

This was an important question in order to determine if our Phase 3 program in alopecia areata should have a 36-week or 52-week primary endpoint treatment period. The data in April showed that continued treatment with REZPEG drove meaningful new responses in patients who had not yet reached SALT score 20 at 36 weeks. 29% and 31% of the 31 patients in the 18 and 24 microgram per kilogram dose arms who entered the blinded treatment extension, respectively, achieved new SALT score 20 responses between weeks 36 and 52 with no new responses in placebo. Across other SALT measurements we looked at, increasing proportions of patients achieved clinically meaningful hair growth thresholds. And importantly, REZPEG achieved the target product profile with 52 weeks of twice monthly dosing.

這是一個重要問題，用以決定我們圓形禿第3期計畫的主要終點治療期間應為36週或52週。4月的資料顯示，對於在36週尚未達到 SALT 分數20的患者，持續以 REZPEG 治療可帶來具意義的新反應。在進入盲態治療延伸的31名患者中，18與24微克/公斤劑量組分別有29%與31%在第36至52週之間新達成 SALT 分數20反應，而安慰劑組未出現新反應。在我們觀察的其他 SALT 指標上，達到具臨床意義毛髮生長門檻的患者比例亦呈增加。且重要的是，REZPEG 以每月兩次給藥、持續52週，即達到目標產品概況（TPP）。

Of note, nearly all of the patients or 94% who entered the blinded 16-week extension period completed treatment to week 52. And this demonstrates that when patients understand the promise of REZPEG to grow hair, they will continue on twice monthly treatment. As Howard stated, our plan is to hold an end of Phase 2 meeting with the FDA this quarter with the EMA scientific advice coming later this year to align on the global registrational path forward in alopecia areata. Our ongoing Phase 2b REZOLVE-AA study also has a 24-week off-treatment observation period for all patients. This data is expected in Q4 2026.

值得注意的是，幾乎所有進入盲態16週延伸期的患者（即94%）皆完成治療至第52週。這顯示當患者理解 REZPEG 促進毛髮生長的潛力時，將願意持續每月兩次的治療。如 Howard 所述，我們計畫於本季與 FDA 召開第2期結束會議，並於今年稍晚取得 EMA 科學諮詢，以就圓形禿的全球註冊路徑達成一致。我們進行中的第2b期 REZOLVE-AA 研究亦包含所有患者24週的停藥後觀察期。預期此資料將於2026年第四季取得。

These data will give us an opportunity to understand what dosing regimens of REZPEG to use beyond 52 weeks in alopecia areata patients and whether we include a less frequent dosing regimen in the registrational program. We believe the 52-week data for REZPEG is well positioned to address several key unmet needs. First, the long-term safety profile is differentiated, including the suitability for chronic use without the safety and monitoring limitations associated with the JAK inhibitor class. Second, the twice monthly dosing profile enables better potential compliance. And third, the opportunity for more durable and deepening efficacy over time.

這些資料將使我們有機會了解：在圓形禿患者中，52週之後 REZPEG 應採用何種給藥方案，以及是否在註冊性計畫中納入較低頻率的給藥方案。我們相信 REZPEG 的52週資料具備良好定位，可回應數項關鍵未被滿足的需求。第一，長期安全性特徵具差異化，包括適合長期慢性使用，且不受 JAK 抑制劑類別相關的安全性與監測限制所影響。第二，每月兩次的給藥特徵可提升潛在依從性。第三，療效隨時間更持久且可進一步加深的機會。

Beyond our two lead indications, we are pursuing the broader potential of the Treg mechanism. In type 1 diabetes, the ongoing Phase 2 study of REZPEG is being sponsored and funded by TrialNet, evaluating REZPEG in patients with new onset Stage 3 type 1 diabetes. TrialNet, as a reminder, is the same consortium that ran the foundational studies for teplizumab, the only approved therapy in this setting, and they bring expertise and a deep commitment to finding better options for patients with this diagnosis.

除了我們的兩個主要適應症之外，我們也在推進 Treg 機制更廣泛的潛力。在第一型糖尿病方面，REZPEG 目前進行中的第 2 期研究由 TrialNet 主導贊助並提供資金，評估 REZPEG 用於新發作的第 3 期第一型糖尿病患者。提醒一下，TrialNet 就是先前執行 teplizumab（此情境下唯一獲核准療法）奠基性研究的同一個聯盟；他們具備專業能力，並且對於為此診斷的患者尋找更佳治療選項有深厚承諾。

In the study, patients are randomized 2:1 to REZPEG or placebo and receive treatment every 2 weeks for 6 months across three sequential age cohorts, starting with adults 18 to 45 and stepping down to patients as young as 12 and then 8 years of age. The primary endpoint is the change in C-peptide levels after a mixed meal tolerance test at 12 months of treatment. We expect initial data from the study in 2027. Given the challenges with administration and safety of teplizumab, REZPEG could be well positioned for new onset type 1 diabetes.

在該研究中，患者以 2:1 隨機分派至 REZPEG 或安慰劑組，並在三個依序進行的年齡隊列中每 2 週接受一次治療、共 6 個月；從 18 至 45 歲成人開始，之後逐步下調至最小 12 歲，再到 8 歲的患者。主要終點為治療 12 個月時，於混合餐耐受試驗後 C-胜肽（C-peptide）水準的變化。我們預期將於 2027 年取得該研究的初步數據。鑑於 teplizumab 在給藥與安全性方面的挑戰，REZPEG 在新發作第一型糖尿病上可能具備良好定位。

We are also planning to initiate a proof-of-concept study in at least one new indication in the second half of 2026 with initial data expected in 2027. We are analyzing the disease settings where a T regulatory mechanism has demonstrated clinical activity, and this will help inform our decision on which indication to prioritize with the goal of achieving an additional data catalyst for REZPEG in 2027.

我們也規劃在 2026 年下半年於至少一個新的適應症啟動概念驗證（proof-of-concept）研究，並預期於 2027 年取得初步數據。我們正在分析哪些疾病情境中，T 調節（T regulatory）機制已展現臨床活性；這將有助於我們決定優先推進哪一個適應症，目標是在 2027 年為 REZPEG 帶來額外的數據催化劑。

And turning to our earlier pipeline programs, NKTR-0165 and NKTR-0166. NKTR-0165 is our TNFR2 agonist antibody, a molecule with very high specificity for signaling through TNFR2 on Tregs to enhance their ability to regulate the immune system. We believe this mechanism has potential across a range of indications, including MS, ulcerative colitis, and vitiligo. In Q1, we announced an academic research collaboration with Dr. Stephen Hauser at UCSF to explore the role of TNFR2 agonism in neurodegeneration, neuroprotection, and cell repair with a focus on patient-derived B-cell models of MS. We look forward to working with Dr. Hauser to inform the future development of this program. We expect to present preclinical data from NKTR-0165 at a scientific conference in the second half of this year.

接著談我們較早期的研發管線項目：NKTR-0165 與 NKTR-0166。NKTR-0165 是我們的 TNFR2 致效（agonist）抗體，對於透過 Treg 上的 TNFR2 進行訊號傳導具有非常高的特異性，可增強其調節免疫系統的能力。我們相信此機制在多種適應症上具有潛力，包括多發性硬化症（MS）、潰瘍性結腸炎，以及白斑症（vitiligo）。在第一季，我們宣布與加州大學舊金山分校（UCSF）的 Stephen Hauser 醫師展開學術研究合作，探索 TNFR2 致效作用在神經退化、神經保護與細胞修復中的角色，並聚焦於以患者來源 B 細胞模型研究 MS。我們期待與 Hauser 醫師合作，以協助本項目未來的開發方向。我們預期將於今年下半年在科學會議上發表 NKTR-0165 的臨床前數據。

Building on the learnings from NKTR-0165, we have designed NKTR-0166, a bispecific molecule that combines a TNFR2 agonist epitope with an antagonist epitope previously validated in rheumatology. This dual mechanism gives NKTR-0166 the potential to modify disease pathogenesis across multiple autoimmune settings, and we are planning IND submissions for at least one of these programs in 2027.

基於 NKTR-0165 的學習成果，我們設計了 NKTR-0166，這是一種雙特異性分子，結合 TNFR2 致效表位（epitope）與先前已在風濕免疫領域驗證的拮抗（antagonist）表位。此雙重機制使 NKTR-0166 具備在多種自體免疫疾病情境中改變疾病致病機轉的潛力；我們規劃在 2027 年就至少其中一個項目提交 IND 申請。

With that, I'll turn it over to Sandy to review our financial results for Q1 2026.

接下來我把時間交給 Sandy，請她回顧我們 2026 年第一季的財務結果。

Thank you, JZ, and good afternoon, everyone. On today's call, I'll review our quarterly financials for the first quarter of 2026 and provide updated cash guidance.

謝謝你，JZ，各位下午好。在今天的電話會議中，我將回顧我們 2026 年第一季的季度財務表現，並提供更新後的現金指引。

We ended the first quarter of 2026 with $731.6 million in cash and investments with no debt on our balance sheet. In the first quarter, we completed an underwritten public offering in sales under our existing ATM facility, resulting in approximately $525 million in net cash proceeds. This does not include an additional $351 million in net proceeds from our April financing. As Howard mentioned earlier, our current cash balance exceeds $1 billion, and we expect to end 2026 with approximately $800 million to $825 million in cash and investments.

截至 2026 年第一季末，我們的現金與投資為 7.316 億美元，資產負債表上沒有負債。第一季期間，我們在既有 ATM（at-the-market）機制下完成承銷公開發行銷售，淨現金募得約 5.25 億美元。此數字不包含我們 4 月融資額外取得的 3.51 億美元淨募資。如 Howard 先前提到，我們目前的現金餘額已超過 10 億美元；我們預期 2026 年底的現金與投資約為 8.00 億至 8.25 億美元。

Now turning to the income statement. Our first-quarter 2026 noncash royalty revenue totaled $10.9 million. Full-year revenue for 2026 is still expected to total $40 million to $45 million. Our R&D expenses were $35.7 million for the first quarter of 2026, and we still anticipate full-year R&D expense to range between $200 million and $250 million, including approximately $5 million to $10 million of noncash depreciation and stock-based compensation expense. As we discussed on our March call, we are still completing the planning and budgeting activities for the REZPEG Phase 3 program. We do, however, expect R&D expense to increase on a quarterly basis in 2026 as these Phase 3 clinical studies are initiated.

接著看損益表。我們 2026 年第一季的非現金權利金收入合計為 1,090 萬美元。2026 全年收入仍預期合計為 4,000 萬至 4,500 萬美元。2026 年第一季研發（R&D）費用為 3,570 萬美元；我們仍預期 2026 全年研發費用介於 2.00 億至 2.50 億美元之間，其中包含約 500 萬至 1,000 萬美元的非現金折舊與以股份為基礎之薪酬費用。如同我們在 3 月電話會議中討論的，我們仍在完成 REZPEG 第 3 期計畫的規劃與預算編列工作。不過，隨著這些第 3 期臨床研究於 2026 年啟動，我們預期研發費用將在 2026 年按季度逐步增加。

Our G&A expenses were $13.4 million for the first quarter. We continue to expect G&A expenses for the full year of 2026 to be between $60 million and $65 million, including approximately $5 million of noncash depreciation and stock-based compensation expense. Noncash interest expense for the first quarter was $7.9 million and is expected to remain at a similar level for the remaining three quarters totaling approximately $30 million to $35 million in 2026. Our net loss for the first quarter was $44.9 million or $1.82 basic and diluted net loss per share. And as I stated earlier, we now expect to end 2026 with between $800 million and $825 million in cash and investments.

我們第一季的管理及一般（G&A）費用為 1,340 萬美元。我們仍預期 2026 全年 G&A 費用介於 6,000 萬至 6,500 萬美元之間，其中包含約 500 萬美元的非現金折舊與以股份為基礎之薪酬費用。第一季非現金利息費用為 790 萬美元，預期在接下來三個季度將維持相近水準，2026 年合計約 3,000 萬至 3,500 萬美元。第一季淨損為 4,490 萬美元，或每股基本及稀釋後淨損 1.82 美元。如我先前所述，我們目前預期 2026 年底的現金與投資將介於 8.00 億至 8.25 億美元。

I'll now turn it over to the operator for Q&A.

接下來我把時間交給接線員進行問答。

(Operator Instructions) Yasmeen Rahimi, Piper Sandler.

(接線員指示) Yasmeen Rahimi，Piper Sandler。

This is Dominic on for Yasmeen Rahimi. Congrats on a great quarter and appreciate all the updates. So we're excited for you to be kicking off the Phase 3 AD program soon. Could you just remind us of what are some of the rate-limiting steps left for those -- I guess, you have the two trials that are starting here shortly. And then could you walk us through some nuggets of detail?

我是 Dominic，代替 Yasmeen Rahimi 發言。恭喜你們交出很棒的一季，也感謝提供所有更新。我們很期待你們很快啟動 AD 第 3 期計畫。能否請你們再提醒一下，對於那些——我想你們有兩項試驗即將在近期啟動——目前還有哪些關鍵的限制步驟（rate-limiting steps）尚待完成？另外也能否帶我們了解一些細節重點？

I know you said there will be some sites in the -- similar to the Phase 2b. So what would the site overlap, I guess, look like for that? Do you have any nuggets of detail on the CRO selection? Anything like that would be very helpful.

我知道你們提到會有一些試驗中心與第 2b 期相似。所以我想問，試驗中心的重疊程度大概會是什麼樣子？在 CRO（委託研究機構）選擇方面，有沒有任何細節重點可以分享？諸如此類的資訊都會非常有幫助。

Dominic, this is Mary. Thank you for your question. We too are very excited to move forward with the Phase 3 study. We right now are activating sites, and we have the final protocol written. In terms of sites, remember in the REZOLVE-AD Phase 2, we enrolled 17% of the patients from the United States and 28% from North America, and we had 67% of the patients came from Europe and 5% from Australia.

Dominic，我是 Mary。謝謝你的提問。我們也非常期待推進第 3 期研究。目前我們正在啟動各試驗中心，且最終版試驗方案已完成撰寫。就試驗中心而言，請記得在 REZOLVE-AD 第 2 期研究中，我們有 17% 的患者來自美國、28% 來自北美；另有 67% 的患者來自歐洲、5% 來自澳洲。

In the Phase 3 program, we're going to have a larger footprint, particularly in the APAC region or the Asian Pacific region. We, in general, expect to enroll roughly 15% to 25% of patients from North America with a similar proportion of patients specifically from the United States as in our Phase 2b trial. And then approximately 40% to 55% of patients will come from Europe and roughly 20% to 30% from APAC. We will have a number of clinical sites that participated in our Phase 2b program, participating in the Phase 3 as well. We had roughly 130 sites that were activated for the Phase 2b trial, and we'll have roughly 150 sites activated for each one of the Phase 3 studies.

在第 3 期計畫中，我們的佈局將更大，特別是在亞太（APAC，Asian Pacific）地區。整體而言，我們預期約有 15% 至 25% 的患者將來自北美，其中來自美國的比例將與我們第 2b 期試驗相近。接著約有 40% 至 55% 的患者將來自歐洲，約 20% 至 30% 來自亞太地區。我們將有多個曾參與第 2b 期計畫的臨床試驗中心，也會參與第 3 期。第 2b 期試驗約啟動了 130 個試驗中心，而第 3 期的每一項研究將約啟動 150 個試驗中心。

Julian Harrison, BTIG.

Julian Harrison，BTIG。

Congratulations on all the progress. On your Phase 3 plan in atopic dermatitis, I'm wondering if you could talk more about the decision to have a separate biologic experience study versus maybe mixing both naive and experienced patients across two larger studies?

恭喜你們取得所有進展。關於你們在異位性皮膚炎的第3期計畫，我想請你們多談談：為何決定針對「曾使用過生物製劑」的族群另外做一項研究，而不是在兩項較大型研究中混合納入生物製劑初治與既往用藥經驗的患者？

Obviously, the cytokine blocking agents that came before us enrolled patients that were biologic naive. And we do feel it is important to be able to compare the results of the REZPEG study on the EASI-75, the IGA, and other secondary endpoints directly to those cytokine blocking agents. And for that reason, we do want to have just a naive patient population.

顯然，在我們之前的細胞激素阻斷劑，其試驗納入的患者都是生物製劑初治。我們也確實認為，能夠將REZPEG研究在EASI-75、IGA以及其他次要終點的結果，直接與那些細胞激素阻斷劑做比較是很重要的。因此，基於這個原因，我們希望只納入初治患者族群。

In terms of the experienced patients, we do believe that we'll have similar efficacy in that population, and that's certainly what has been seen in the lebrikizumab trial that evaluated patients who had previously been treated with Dupixent. The EASI-75 and the IGA score was similar to what we've seen with lebrikizumab in the naive patient population. However, we have not yet studied the biologic experience in the JAK inhibitor experienced patients yet. Likewise, there may be different clinical sites that has a larger patient population with the biologic experienced patients, and it will be easier for us to find the footprint and enroll those and activate those sites for the experienced study.

至於有用藥經驗的患者，我們相信在該族群中也會有相近的療效；而這點也確實在lebrikizumab試驗中看到，該試驗評估了先前曾接受Dupixent治療的患者。其EASI-75與IGA分數與我們在初治患者族群中看到的lebrikizumab結果相近。不過，我們尚未研究在曾使用JAK抑制劑的患者中之生物製劑用藥經驗。同樣地，某些臨床試驗中心可能擁有較多曾使用生物製劑的患者族群，對我們而言也更容易找到合適的據點、完成收案並啟動這些中心來進行有經驗族群的研究。

So we think operationally, there are advantages to do it. And likewise again having the ability to compare directly to Dupixent and lebrikizumab and trilkizumab that just enrolled the naive patients, we believe, will be an advantage.

因此我們認為在營運執行上這樣做有其優勢。同樣地，再次強調，能夠直接與只納入初治患者的Dupixent、lebrikizumab與trilkizumab進行比較，我們相信也會是一項優勢。

Jay Olson, Oppenheimer.

Jay Olson，Oppenheimer。

I'll add my congrats on all the progress, including getting ZENITH-AD up and running in the near term. We had a question on alopecia areata. Can you please provide some updates on your thinking around the Phase 3 study design for REZPEG in AA and especially in terms of the enrollment criteria in terms of age of patients and baseline SALT score and then whether or not you think a single Phase 3 study is sufficient?

我也要補上對你們所有進展的祝賀，包括近期讓ZENITH-AD啟動並運行。我們有一個關於圓形禿（alopecia areata）的問題。能否請你們更新一下你們對REZPEG在AA第3期研究設計的想法，特別是收案條件，例如患者年齡與基線SALT分數，以及你們是否認為單一項第3期研究就足夠？

We are having our end of Phase 2 meeting with the FDA this quarter. So we will have more information following the regulatory meeting that we're having. That being said, the Phase 3 study design will be 52 weeks. We will evaluate REZPEG 24 micrograms per kilogram versus placebo.

我們本季將與FDA召開第2期結束（End-of-Phase 2）會議。因此在這場法規會議之後，我們會有更多資訊。話雖如此，第3期研究設計將為期52週。我們將評估REZPEG 24微克/公斤相較於安慰劑。

We think a study roughly the size of 600 patients and one single study should be accepted by the FDA. The reason we believe this is that Pfizer did run one Phase 3 study for Litfulo, their JAK inhibitor, and the FDA did accept one single Phase 3 study. So we have asked the FDA to confirm this precedent would also be applied to our program.

我們認為一項約600名患者規模、且僅一項單一研究，應可被FDA接受。我們之所以這麼認為，是因為Pfizer針對其JAK抑制劑Litfulo確實只進行了一項第3期研究，而FDA也接受了單一第3期研究。因此我們已請FDA確認，這項先例也會同樣適用於我們的計畫。

In terms of age, patients would be 12 years and older. And in terms of baseline SALT score, we will enroll patients with severe and very severe alopecia areata, which is a SALT score of 50 or above. Many people have asked us, could we develop REZPEG for patients with moderate alopecia areata? And we do think the answer to that question is yes. However, that would come after we would have an approval for the severe and very severe population. And of course, JAK inhibitors are not appropriate for that patient population given the black box warnings that Howard referred to and the difficulty in managing patients on JAK inhibitors. However, we think there's a huge opportunity for REZPEG in that patient population as well.

在年齡方面，患者將為12歲以上。在基線SALT分數方面，我們將納入重度與極重度圓形禿患者，也就是SALT分數50以上。很多人問我們：REZPEG是否能開發用於中度圓形禿患者？我們確實認為答案是可以。不過，那會是在我們先取得重度與極重度族群核准之後再進行。當然，鑑於Howard提到的黑框警語，以及在JAK抑制劑治療下管理患者的困難，JAK抑制劑並不適合該患者族群。然而，我們認為REZPEG在該患者族群同樣有非常大的機會。

Cha Cha Yang, Jefferies.

Cha Cha Yang，Jefferies。

This is Cha Cha on for Roger Song. So I have a question about your earlier pipeline program, especially in T1D. Can you just tell us more about the collaboration with TrialNet and what that looks like and particularly what rights that Nektar has that data into future development rights?

我是Cha Cha，代替Roger Song提問。我有一個關於你們較早期管線計畫的問題，特別是在第一型糖尿病（T1D）。你們能否多談談與TrialNet的合作內容、合作模式長什麼樣子，以及特別是Nektar對於這些資料在未來開發上的權利是什麼？

And then my second question related to that is, can you tell us more about the baseline characteristics for the T1D study and how they might compare to the PROTECT study?

另外第二個相關問題是：你們能否多談談T1D研究的基線特徵，以及它們可能如何與PROTECT研究相比？

Sure. So in that collaboration with TrialNet, which is part of the NIH and the NIDDK, the TrialNet and the TrialNet consortium is -- besides funding is also executing the study. So we work together on the design of the study protocol. It leverages all of their expertise, including the really large data set that they have on the change in C-peptide levels in patients that are newly diagnosed, really this patient population.

當然。在與TrialNet的合作中，TrialNet隸屬於NIH與NIDDK；TrialNet及其聯盟除了提供資金外，也負責執行該研究。因此我們共同合作設計研究方案（protocol）。這也運用了他們所有的專業能力，包括他們在新診斷患者（也就是這類患者族群）C-胜肽（C-peptide）變化方面所累積的龐大資料集。

We also work closely with the lead investigators. And even on our call when we announced the start of the collaboration, the two lead PIs joined that call with us to present the study and the concept behind REZPEG in this indication. So we'll be working with them, but they're responsible for really driving the execution of the study.

我們也與主要研究者密切合作。甚至在我們宣布合作啟動的電話會議上，兩位主要PI也與我們一同參與，介紹該研究以及REZPEG在此適應症背後的概念。因此我們會與他們合作，但他們確實負責推動研究的實際執行。

The patient population is very, very typical in these studies. So there are patients that are within 100 days of their first diagnosis of type 1 diabetes. So these are patients that have really just had their first clinical episode of disease, and they're enrolled into the study within 100 days. So a very typical patient population for these kind of new onset stage 3, type 1 studies.

該患者族群在這類研究中非常、非常典型。也就是在第一型糖尿病首次診斷後100天內的患者。因此這些患者基本上剛出現第一次臨床發病事件，並在100天內納入研究。這是此類新發（new onset）第3期（stage 3）第一型糖尿病研究中非常典型的患者族群。

And in terms of the rights, Nektar maintains the rights to REZPEG and the future development in type 1 diabetes that would come subsequent to this if this study is possible.

至於權利方面，Nektar保有REZPEG以及未來在第一型糖尿病領域後續開發的權利；若本研究可行，後續開發將在此基礎上推進。

Samantha Semenkow, Citi.

Samantha Semenkow，Citi。

I just have one on the upcoming off-treatment data sets that we're expecting for both atopic derm and alopecia areata. How should we be thinking about what good data would look like in these readouts? Is there a bar for EASI maintenance, for example, or a SALT score maintenance that you would like to see from each of these or some other metrics that you're tracking closely?

我只有一個問題，關於我們預期在異位性皮膚炎與圓形禿兩個適應症即將公布的停藥後（off-treatment）資料集。在這些讀出中，我們應該如何思考「好的數據」會長什麼樣子？例如，是否有你們希望看到的EASI維持門檻，或SALT分數維持門檻，或是你們正在密切追蹤的其他指標？

So I think I'll start with alopecia areata first. We continue to dose those 27 patients for an additional 16 weeks, and we just shared those data. And as you saw, there were 8 new SALT score -- 8 new patients that reached a SALT score less than or equal to 20. The big question that we have is what type of maintenance dosing will be best suited for these patients that have achieved a SALT score less than 20 or have 80% of their hair regrowth. We figured that out in our atopic dermatitis program, the ideal maintenance dosing after a 16- or 24-week induction period should be 1 month and 3 months.

我想我先從圓形禿開始。我們持續對那27名患者額外給藥16週，而我們也剛分享了那些數據。如你所見，又新增了8名患者達到SALT分數小於或等於20。我們最大的問題是：對於已達到SALT分數小於20、或已達到80%毛髮再生的患者，哪一種維持劑量（maintenance dosing）最合適。我們在異位性皮膚炎計畫中已經釐清：在16或24週誘導期（induction period）後，理想的維持給藥頻率應為每1個月與每3個月。

In terms of alopecia areata, after 52 weeks of treatment, we don't yet know what the maintenance dosing should be. And so for that off-treatment data that we're going to have at the end of this year, it's going to be highly informative to us to understand how we should continue to dose patients in the alopecia areata program after 52 weeks of treatment, given 24 micrograms per kilogram every 2 weeks.

就圓形禿而言，在治療52週之後，我們目前仍不確定維持給藥應該如何安排。因此，我們預計在今年底取得的停藥後數據，將為我們提供非常關鍵的資訊，幫助我們理解：在以每2週24微克/公斤治療52週之後，圓形禿計畫中應如何繼續對患者給藥。

In terms of the data from the REZOLVE-AD study, you're absolutely right. We'll continue to follow the durability of those patients' responses in those patients who achieved an EASI-75 and EASI-90 and IGA 0 and 1, and we'll continue to look at the durability of those responses. As we saw with Q monthly dosing and Q 3 months dosing, we had exceptional durability, and we also saw deepening of responses.

就 REZOLVE-AD 研究的數據而言，你說得完全正確。我們將持續追蹤那些達到 EASI-75 與 EASI-90 以及 IGA 0 與 1 的患者之反應持久性，並會繼續評估這些反應的耐久度。如同我們在每月一次（Q monthly）與每三個月一次（Q 3 months）給藥所看到的，我們呈現出卓越的持久性，同時也觀察到反應進一步加深。

Now with the off-treatment, we'll be able to determine are patients able to maintain those EASI-100 responses, the 30% of patients that achieved that and the IGA 0 and 1 responses. And remember, we had roughly 60% of patients who had an EASI-75 or vIGA at the time of rerandomization achieving an IGA of 0 and 1. So we'll be very eager to see the durability of maintaining the EASI-75, the EASI -100, and vIGA-01. I think this will be highly informative again to understand the dosing frequency for these patients after they're treated with 52 weeks of treatment.

現在在停藥（off-treatment）情境下，我們將能判定患者是否能維持那些 EASI-100 反應——也就是達到該結果的 30% 患者——以及 IGA 0 與 1 的反應。並且請記得，在重新隨機分派（rerandomization）時點，約有 60% 的患者達到 EASI-75 或 vIGA，且其中達到 IGA 0 與 1。因此，我們將非常期待看到維持 EASI-75、EASI-100 與 vIGA-01 的持久性。我認為這將再次提供高度資訊性，幫助我們理解這些患者在接受 52 週治療後的給藥頻率。

So you're absolutely right. The standard endpoints that we use for clinical trials will also be the endpoints that we'll look at in the off-treatment timeframe.

所以你說得完全正確。我們在臨床試驗中使用的標準終點，也將是我們在停藥期間所要觀察的終點。

Marc Frahm, TD Cowen.

Marc Frahm，TD Cowen。

Congrats on all the progress getting the trials designed. Maybe just on that bio-experienced patient study in atopic dermatitis. Can you just walk through kind of how you're defining bio-experience there? Will patients be required to have overtly failed therapy? Or could they have discontinued for any other reason?

恭喜你們在試驗設計推進上取得所有進展。我想問一下關於異位性皮膚炎的生物製劑既往治療（bio-experienced）患者研究。你們能否說明一下你們如何定義這裡的 bio-experience？患者是否必須明確治療失敗？或者也可能因其他任何原因而停用？

Just how long do they have to have been off therapy, things like that? And will that include JAK experienced patients or just focused on the IL-413 pathway?

另外，他們需要停用治療多久之類的條件？以及這是否會納入有 JAK 用藥經驗的患者，還是只聚焦於 IL-413 路徑？

So all the candidates have to require systemic therapy. So they have to have a history of atopic dermatitis for at least 12 months, and they had to have had an inadequate response to topical medications. And then in addition to that, these patients have to have then had either a biologic or a JAK inhibitor. So we will be enrolling patients that have also been on JAK inhibitors.

所以所有候選者都必須需要系統性治療。也就是說，他們必須至少有 12 個月的異位性皮膚炎病史，且對外用藥物反應不足。此外，這些患者還必須曾使用過生物製劑或 JAK 抑制劑。因此，我們也會納入曾使用 JAK 抑制劑的患者。

In terms of washouts for biologic, patients will have to have been off treatment for 12 weeks or 5 half-lives, whichever is longer. And then for JAK inhibitors, there will be a washout of 4 weeks. The eligibility criteria for moderate to severe atopic dermatitis is very similar for both studies. Of course, patients have to have an EASI score of 16 or higher, a body surface area of 10% or more and have an entry of a vIGA -- or excuse me, an IGA of 3 or 4.

就生物製劑的洗脫期（washout）而言，患者必須停藥 12 週或 5 個半衰期，以較長者為準。而對於 JAK 抑制劑，洗脫期為 4 週。中重度異位性皮膚炎的納入標準在兩項研究中非常相似。當然，患者必須 EASI 分數達 16 分或以上、受累體表面積（BSA）達 10% 或以上，並且入組時 vIGA——抱歉，是 IGA——必須為 3 或 4。

Okay. That's very helpful. Do you think you need to be successful in all three trials to get approved? Or is two out of three enough for approval do you think?

好的。這非常有幫助。你認為要獲得核准是否需要三項試驗都成功？或者你覺得三項中有兩項成功就足夠核准？

Yes. I think that this is a great regulatory question. And as we unblind the data and have conversations with our regulatory advisers, I do believe that showing efficacy in two well-controlled randomized trials would be sufficient for regulatory approval, but we again will have to have those conversations with the FDA at the time of our BLA submission.

是的。我認為這是一個很好的法規問題。隨著我們解盲數據並與法規顧問討論，我確實相信，在兩項設計良好、對照嚴謹的隨機試驗中顯示療效，應足以支持法規核准；但我們仍需在提交 BLA 時與 FDA 進行相關溝通。

Mayank Mamtani, B. Riley.

Mayank Mamtani，B. Riley。

Congrats on the progress. Just on the prior comment on the AD off-therapy durability data. Just curious, how do you expect an endpoint like EASI-100 to sort of evolve over time there? And then on the earlier stage pipeline, the 0166 bispecific program, JZ, just was curious how you're thinking of developing that maybe relative to 0165? And maybe just remind us what are the key milestones to watch out for those two programs?

恭喜進展。關於先前提到的 AD 停藥後持久性數據，我有個問題。我想了解像 EASI-100 這樣的終點，你預期在那段時間會如何隨時間演變？另外在較早期的產品線方面，0166 雙特異性（bispecific）計畫，JZ，我想請教你們如何思考其開發策略，可能相對於 0165 而言？也請提醒我們，這兩個計畫接下來值得關注的關鍵里程碑是什麼？

I can start with the last question first, Mayank. So for 0166, so as we mentioned, that it's a bispecific, right? That contains a TNFR2 agonist on one arm and then a validated target for rheumatology indications on the other arm. So our indications are definitely in the rheumatology setting. And then we have the opportunity to have basically multiple mechanisms, right, that we bring forward on the cell as well as adding a TNFR2 second component for a potential differentiating novel approach to treating rheumatology diseases.

Mayank，我先從最後一個問題開始。關於 0166，如我們提到的，它是一個雙特異性分子，對吧？其中一個臂帶有 TNFR2 致效劑（agonist），另一個臂則是針對已被驗證、用於風濕免疫適應症的標的。因此，我們的適應症明確是在風濕免疫領域。同時，我們也有機會在細胞層面帶來基本上多重機制，並加入 TNFR2 的第二個組件，作為一種可能具差異化、創新的風濕免疫疾病治療方式。

In terms of the main milestones that we have across that program is we have IND-enabling studies around 0165. And then the 0166 program is a little bit further behind, but it's also undergoing those same IND-enabling studies as well.

就該計畫的主要里程碑而言，我們正在針對 0165 進行 IND 申請前的支持性研究（IND-enabling studies）。而 0166 計畫稍微落後一些，但也同樣在進行這些 IND-enabling 研究。

And I'll turn it over to you, Mary, for the other question.

接下來我把另一個問題交給 Mary。

So as you know, we did publish data from our Phase 1b in Nature Communications, and this was published in 2024. And what we did show is that patients were dosed with the highest dose of REZPEG 24 micrograms per kilogram. And then those patients after 12 weeks of treatment were off therapy for a total of 9 months. And we did see that these patients were able to maintain their EASI-75, and there was remarkable durability, and you can see that in the publication, so if we replicate the data from the early Phase 1, we would see durability for potentially 9 to 12 months off therapy.

如你所知，我們已在《Nature Communications》發表了第一期 1b 的數據，發表於 2024 年。我們所顯示的是，患者接受了最高劑量的 REZPEG 24 微克/公斤。之後，這些患者在治療 12 週後停藥，總計停藥 9 個月。我們確實看到這些患者能維持 EASI-75，且持久性非常顯著；你可以在該論文中看到。因此，如果我們能複製早期第一期的數據，我們可能會看到停藥後可維持 9 到 12 個月的持久性。

Again, I think the goal here is to find a treatment regimen that's highly differentiating from the current available therapies. And as you know with Dupixent, patients have to take an injection every two weeks indefinitely. And so we really believe if we can get to a dosing regimen of REZPEG that's monthly or every quarterly, just like SKYRIZI 4 times a year, this will be a huge advantage for patients and quite a transformation in this field.

再次強調，我認為這裡的目標是找到一種相較於目前可用療法高度差異化的治療方案。而如你所知，使用 Dupixent 的患者必須無限期地每兩週注射一次。因此我們確實相信，如果我們能把 REZPEG 的給藥方案做到每月一次或每季一次，就像 SKYRIZI 一年 4 次，這將對患者是巨大的優勢，也會為這個領域帶來相當大的轉變。

Hopefully, the data will also show durability off treatment. And therefore, if patients go for longer than three months without dosing, especially if they get to an EASI-100 complete clearance of disease and have this level of durability, this will be a huge advantage for patients. I think we're all eager to see the data and to see the length of time that patients can maintain their IGA 0 or the EASI-75, EASI-90, and EASI-100. So we really look forward to having those data in the first quarter of next year.

我們也希望數據能顯示停藥後仍具持久性。因此，如果患者在不給藥的情況下能超過三個月，特別是若能達到 EASI-100 的疾病完全清除並具備這種程度的持久性，這將對患者是巨大的優勢。我想我們都很期待看到數據，以及患者能維持 IGA 0 或 EASI-75、EASI-90 與 EASI-100 的時間長度。因此，我們非常期待在明年第一季取得這些數據。

Arthur He, HC Wainwright.

Arthur He，HC Wainwright。

Congrats on the progress. So I had two quick questions on alopecia areata program. So first, could you remind us how you picked the 24-week off-treatment period at the first place, why not longer? And also, for the Phase 3 study, are you guys contemplating to include JAK inhibitor experienced or refractory patients in the Phase 3 study for alopecia areata?

恭喜進展。我有兩個關於圓形禿（alopecia areata）計畫的快速問題。第一，能否提醒我們當初為何選擇 24 週的停藥觀察期，為什麼不更長？第二，對於第三期研究，你們是否考慮在圓形禿的第三期試驗中納入有 JAK 抑制劑用藥經驗或對其難治（refractory）的患者？

So we chose the 24-week off-treatment period because you may know with JAK inhibitors, patients start to lose hair relatively quickly. And so we felt like that was a sufficient amount of time to potentially see a differentiation between JAK inhibitors and REZPEG. And in terms of the Phase 3, we are going to go with patients who are JAK inhibitor naive. However, there are multiple other ways to evaluate REZPEG in a patient population that is JAK inhibitor experienced. We do believe that in this particular indication, REZPEG could be a first-line therapy.

因此我們選擇了 24 週的停藥觀察期，因為如各位所知，使用 JAK 抑制劑的患者會相對很快開始掉髮。因此我們認為這段時間足以有機會觀察到 JAK 抑制劑與 REZPEG 之間的差異化。至於第 3 期試驗，我們將納入未曾使用過 JAK 抑制劑（JAK inhibitor naive）的患者。不過，仍有多種其他方式可在曾使用過 JAK 抑制劑（JAK inhibitor experienced）的患者族群中評估 REZPEG。我們確實相信，在這個特定適應症中，REZPEG 可能成為第一線治療。

And for those of you who were able to listen to our presentation for the 52-week data in alopecia areata, all of our KOLs said that the vast majority of patients and in fact Jonathan Silverberg said 90% of his patients would use REZPEG in the first-line setting. So we do and we are positioning REZPEG in the first-line setting for alopecia areata. And we do believe the drug will be effective as well in patients who have already experienced a JAK inhibitor and we'll find another pathway to explore REZPEG and evaluate REZPEG in that patient population as well.

而對於各位有收聽我們在圓形禿（alopecia areata）52 週數據簡報的人，我們所有的 KOL 都表示，絕大多數患者——事實上 Jonathan Silverberg 表示他有 90% 的患者——會在第一線治療情境中使用 REZPEG。因此，我們確實正在將 REZPEG 定位於圓形禿的第一線治療。我們也相信，對於已經使用過 JAK 抑制劑的患者，該藥物同樣會有效；我們會找到另一條途徑來探索並在該患者族群中評估 REZPEG。

Andy Hsieh, William Blair.

Andy Hsieh，William Blair。

Just follow up on Jay's question previously. Mary, you mentioned about having to basically conduct a Phase 3 trial in alopecia and getting a label before conducting a trial in a moderate population. So I'm curious, one, do you have to go back to a Phase 2 or you can start a Phase 3 after that? And then the other one is really about understanding FDA's pushback. Is it -- are they not comfortable with the safety database, especially now you have hundreds of patients in safety database?

我想接續追問一下先前 Jay 的問題。Mary，你提到基本上必須先在圓形禿完成第 3 期試驗並取得標籤，之後才能在中度族群進行試驗。所以我好奇，第一，你們是否必須回到第 2 期，還是之後可以直接啟動第 3 期？第二個問題是想了解 FDA 的反對點。是——他們對安全性資料庫不夠放心嗎？尤其是現在你們的安全性資料庫已經有數百名患者？

So just I'm curious about why there's such a regulatory pushback in a moderate population.

所以我只是好奇，為什麼在中度患者族群上會有這麼大的監管阻力。

Thanks, Andy. So we do have to speak to the agency about the moderate population. But after speaking with our steering committee members, the placebo effect in -- for alopecia areata for patients who have severe and very severe disease is very low. For SALT 20, it's single digits between 2% and 5%. So running a clinical trial where the placebo effect for your primary efficacy endpoint is low and testing the same population as in our Phase 2b AA study gives us a high probability of technical success for our registrational program.

謝謝你，Andy。我們確實需要就中度患者族群與主管機關溝通。但在與我們的指導委員會成員討論後，對於圓形禿中重度與極重度患者，安慰劑效應非常低。以 SALT 20 來看，只有個位數，大約在 2% 到 5% 之間。因此，進行一項臨床試驗——其主要療效終點的安慰劑效應很低，且測試的族群與我們第 2b 期 AA 研究相同——讓我們的註冊性計畫具有很高的技術成功機率。

Now that being said, in the moderate patient population per our KOLs and our steering committee, the placebo effect could be higher in the population of patients that have, say, a SALT score that's actually less than 50, so in the 30 to 50 range. So we believe that the best path forward is to go with the clear regulatory precedent where there is a clear endpoint for the patient population that's with a SALT 50 or above. And we will have a conversation with the FDA about the moderate patient population. We have not gotten feedback yet through our end of Phase 2 or regarding the moderate population. So we have not received any pushback.

話雖如此，根據我們的 KOL 與指導委員會，在中度患者族群中，安慰劑效應可能更高；例如 SALT 分數其實低於 50 的患者，也就是 30 到 50 的區間。因此我們認為，最佳前進路徑是遵循明確的監管先例：針對 SALT 50 或以上的患者族群，採用明確的終點。我們也會就中度患者族群與 FDA 進行討論。我們尚未在第 2 期結束會議（end of Phase 2）或針對中度族群收到回饋。因此我們尚未收到任何反對意見。

We just haven't had the conversation yet, Andy.

只是我們還沒有進行那場對話而已，Andy。

Jessica Fye, JPMorgan.

Jessica Fye，JPMorgan。

This is Jose for Jess. It seems like you have much of the plan in place for the Phase 3 in alopecia. So just wondering if you can, what are the points that you can hammer -- you want to hammer out with FDA at the end of Phase 2 meeting?

我是 Jose，代替 Jess 提問。看起來你們對圓形禿第 3 期的計畫已經大致就緒。所以想請問，在第 2 期結束會議上，你們希望與 FDA 敲定哪些重點？

Of course, a lot has come up about can you run one Phase 3 clinical trial versus two? And again, there's precedent for one Phase 3 clinical trial for this indication. As we mentioned, Pfizer was able to have their JAK inhibitor, Litfulo, approved with one Phase 3. So I would say that's probably the most important question and answer that we want to have from the FDA after our end of Phase 2 meeting.

當然，大家討論很多的是：你們能否只做一項第 3 期臨床試驗，而不是兩項？而且，如我們所提，這個適應症確實有只做一項第 3 期臨床試驗的先例。例如輝瑞就能以一項第 3 期試驗讓其 JAK 抑制劑 Litfulo 獲得核准。所以我會說，這大概是我們在第 2 期結束會議後最重要、希望從 FDA 得到的問題與答案。

In addition, we have submitted our study design, and we want to make sure that the FDA agrees with the powering of our trial and the eligibility criteria. And I think the third and also important point is the totality of our safety data. As Andy Hsieh just brought up, we do have a very large safety database with over 1,000 patients dosed in an inflammatory skin disease. And so we also want alignment with the agency over the safety database for alopecia areata when we file our BLA.

此外，我們已提交研究設計，我們希望確認 FDA 同意我們試驗的樣本數/統計把握度（powering）以及納入條件。我認為第三點同樣重要的是我們安全性資料的整體性（totality）。正如 Andy Hsieh 剛才提到的，我們擁有非常龐大的安全性資料庫，在發炎性皮膚疾病中已有超過 1,000 名患者接受給藥。因此，當我們提交 BLA 時，也希望就圓形禿的安全性資料庫與主管機關達成一致。

So those are three of the most important topics that we want to have clarity and alignment with the agency.

以上就是我們希望與主管機關釐清並取得一致的三個最重要議題。

Thank you. And I'm showing no further questions from our phone lines. I'd now like to pass the conference back to Howard Robin for any closing remarks.

謝謝。我這邊顯示電話線上已無其他提問。接下來我想把會議交回給 Howard Robin，請他做結語。

Well, before I end the call today, I want to comment that Sandy, our current Interim CFO, will be retiring on May 15. And as our Interim Chief Financial Officer, Sandy has played an instrumental role in supporting Nektar over the last three years, and we're very grateful for her contributions and will miss her.

在我結束今天的電話會議之前，我想補充說明：我們現任的臨時財務長（Interim CFO）Sandy 將於 5 月 15 日退休。作為我們的臨時財務長，Sandy 在過去三年中對支持 Nektar 發揮了關鍵作用，我們非常感謝她的貢獻，也會想念她。

For continuity, we're bringing in another partner from FLG Partners, Linda Rubinstein, who will take over Sandy's role as Interim CFO. Linda has 35 years of experience and has served as interim or permanent CFO, leading finance and financial reporting at a number of biotechnology companies, including Solexa, Five Prime, True North, and most recently, Adverum. Her early career was in M&A banking. And all of us do wish Sandy the very best in her retirement.

為了維持延續性，我們將從 FLG Partners 引進另一位合夥人 Linda Rubinstein，由她接任 Sandy 的臨時財務長職務。Linda 擁有 35 年經驗，曾在多家生技公司擔任臨時或正式 CFO，並領導財務與財務報導工作，包括 Solexa、Five Prime、True North，以及最近的 Adverum。她職涯早期從事併購（M&A）投資銀行業務。我們也衷心祝福 Sandy 退休生活一切順利。

I want to thank everyone today for joining us and for your continued support. We really appreciate it. I also want to thank our employees who have worked tirelessly to advance our research in pursuit of novel treatment options for patients. And together, we've transformed our scientific hypothesis into real and potentially meaningful therapeutic options.

我要感謝今天所有與會者的參與，以及各位持續的支持。我們非常感激。我也要感謝我們的員工，他們不懈努力推進研究，以追求為患者提供新穎的治療選項。我們也一起把科學假說轉化為真實且可能具有重要意義的治療選擇。

We look forward to initiating our Phase 3 studies in atopic dermatitis in the coming months and advancing alopecia areata into Phase 3 as well. And we will also be exploring other REZPEG potential in T-cell-mediated diseases. So we thank you very much for joining us today and stay tuned.

我們期待在未來幾個月啟動異位性皮膚炎的第 3 期研究，並同時推進圓形禿進入第 3 期。我們也將探索 REZPEG 在其他 T 細胞介導疾病中的潛力。非常感謝各位今天的參與，敬請持續關注。

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.

謝謝。今天的電話會議到此結束。感謝各位的參與。您現在可以掛線。祝各位有美好的一天。